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Donepezil (Ariceptģ) Reduces Falls in People with Parkinsonís

- Nov 11 2010

In a preliminary study, taking the drug donepezil (Aricept®) reduced the number of falls by half among a small group of people with Parkinson’s disease (PD) who had trouble with balance and experienced frequent falls. The drug already is an approved therapy for the cognitive symptoms of Alzheimer’s disease, and may be helpful for cognitive symptoms in PD. The study appears in the October 2010 issue of Neurology.

Among the movement symptoms of Parkinson’s, balance and gait difficulties are perhaps the most difficult to treat. While carbidopa/levodopa (Sinemet®), the gold-standard therapy for motor symptoms, can reduce some falls in some people with PD, there is generally not a therapy to protect people with Parkinson's from falls. As many as two-thirds of people with PD experience falls each year. Both injuries and the fear of falling can limit the daily activities of a person with PD.

Medications that block the neurotransmitter acetylcholine were among the first medications to be used for Parkinson’s, even before carbidopa/levodopa. However, earlier studies have linked low brain levels of the neurotransmitter acetylcholine to falls. Parkinson’s causes people to lose neurons that are responsible for producing this chemical. Donepezil works by boosting acetylcholine levels. While previously shown to increase PD tremor, the authors of the new study, led by Kathryn A. Chung, M.D., at the Oregon Health & Science University, reasoned that donepezil might improve balance and reduce falls in people with PD.

A total of 23 people with PD who reported falling or nearly falling more than twice a week enrolled in the double-blinded study. Participants took donepezil for six weeks and a placebo for six weeks, with a three-week break in between. The average participant age was 68; 15 were male; and six had undergone deep brain stimulation.

Results

Study participants fell about half as often when taking Donepezil as compared to a placebo.

Participants who fell the most before the study had the most improvement after six weeks on donepezil.

The number of near falls was the same whether participants were taking Donepezil or placebo.

About a third of participants experienced drug side effects including nausea, sweating and insomnia, and three participants dropped out due to medication side effects.

Two participants who experienced freezing episodes did not benefit from donepezil.

What Does it Mean?

Falls are a serious complication of PD. People with PD may be at risk for falling for a variety of reasons including slower reflexes, postural instability, inattentiveness, light headedness and dyskinesia. Carbidopa-levodopa can help only in a subset of these causes, and not infrequently, additional treatment is needed. Although these results are encouraging, studies with larger numbers of participants will be needed to test donepezil as a therapy that reduces falls. Further research also may help uncover the mechanism by which donepezil may help to prevent falls. This would allow the clinicians to prescribe donepezil to those who fall because of that mechanism (for example, if donepezil improves inattentiveness, to provide it for those who fall because of that reason).